MADRID, Spain (AP)_ Top-seeded Mary Pierce received a jolt in her preparations for the French Open, losing in straight sets Wednesday to a woman with a No. 255 ranking.

Germana de Natale of Italy eliminated the world's No. 6 player 6-4, 6-4 in the first round of the $170,000 Madrid Open.

Pierce's upset highlighted a day in which the top three seeded women were beaten in the clay-court event.

Virginea Ruano of Spain beat No. 2 Amy Frazier of the United States 6-2, 6-3, and Fabiola Zuluaga of Colombia defeated No. 3 Ai Sugiyama of Japan 6-2, 6-4.

Pierce was replacing last year's winner, Lindsay Davenport. Davenport, ranked No. 2, pulled out at the last moment because of a back injury.

Last year's runner-up, Paola Suarez, dropped out of the tournament because of a back injury after playing two sets against Australia's Nicolase Pratt in their second-round match.

Sanchez's injury was not deemed serious, but the sixth-seeded Argentine did not want to risk further injury with the French Open starting Monday.

Zuluaga advanced to the quarterfinals against Sweden's Asa Carlsson, who defeated Maureen Drake of Canada 6-2, 6-0. Gala Leon of Spain defeated Rita Grande of Italy 6-4, 6-4.